Myhre syndrome (MS) is a connective tissue disorder with multisystem involvement with or without intellectual disability. In most cases SMAD4 mutations are reported. To date, 55 individuals have been molecularly confirmed. Autism has been proposed among associate clinical features of MS but no standardized diagnosis was available in previous cases. We report a case of a 25-year-old man with a pathogenic heterozygous SMAD4 missense mutation affecting residue Arg(496) (SMAD4:p.Arg496Cys). Clinical findings are consistent with MS, commorbid with affective disorder and High Functioning Autism Spectrum Disorder confirmed by a standardized assessment procedure. The thorough clinical assessment of cases with syndromes such as MS can extend our knowledge on both the phenotypic characteristics of the syndrome and the genetic basis of autism.

BACKGROUND : Despite its importance within behavioural intervention, it remains unclear how best to achieve high procedural fidelity. This paper reviewed studies on improving procedural fidelity of behavioural interventions for individuals with intellectual and developmental disabilities (IDD). METHOD : A systematic literature search was conducted, which identified 20 studies meeting inclusion criteria. Data were extracted on study design, participant characteristics, intervention, target behaviours, effect sizes, maintenance, generalization and social validity. A quality rating was also applied. RESULTS : A total of 100 participants took part in the included studies. Most participants were teachers working with children in school settings. There was a significant positive correlation between level of procedural fidelity and client outcomes. Feedback was the most commonly employed intervention to improve procedural fidelity. CONCLUSIONS : More research should be conducted in environments with high levels of variability such as community homes to determine how to reach and maintain high levels of procedural fidelity.

Rett syndrome (RTT), a rare neurodevelopmental disorder caused by mutations in the MECP2 gene, is typified by profound cognitive impairment and severe language impairment, rendering it very difficult to accurately measure auditory processing capabilities behaviorally in this population. Here we leverage the mismatch negativity (MMN) component of the event-related potential to measure the ability of RTT patients to decode and store occasional duration deviations in a stream of auditory stimuli. Sensory memory for duration, crucial for speech comprehension, has not been studied in RTT.High-density electroencephalography was successfully recorded in 18 females with RTT and 27 age-matched typically developing (TD) controls (aged 6-22 years). Data from seven RTT and three TD participants were excluded for excessive noise. Stimuli were 1 kHz tones with a standard duration of 100 ms and deviant duration of 180 ms. To assess the sustainability of sensory memory, stimulus presentation rate was varied with stimulus onset asynchronies (SOAs) of 450, 900, and 1800 ms. MMNs with maximum negativity over fronto-central scalp and a latency of 220-230 ms were clearly evident for each presentation rate in the TD group, but only for the shortest SOA in the RTT group. Repeated-measures ANOVA revealed a significant group by SOA interaction. MMN amplitude correlated with age in the TD group only. MMN amplitude was not correlated with the Rett Syndrome Severity Scale. This study indicates that while RTT patients can decode deviations in auditory duration, the span of this sensory memory system is severely foreshortened, with likely implications for speech decoding abilities.

This study aims to translate the Brief Autism Mealtime Behaviour Inventory (BAMBI) questionnaire to Brazilian Portuguese, in order to provide a tool to be used in clinic routine that encourages the evaluation of the feeding behaviour of patients with Autism Spectrum Disorder (ASD). The final sample contained 410 participants, the mean age was 9.58 +/- 1.2 and the majority of participants were male (95%). Validation of this questionnaire allows a structured evaluation for this population to be integrated not only into the clinical routine but also to help parent’s interventions about the eating problems and possible consequences. This is of utmost importance, since parents are reporting the nutritional aspects more often, and studies indicate that up to 80% of ASD patients may present feeding behavior problems.

Previous studies have shown complications of pregnancy, often examined in aggregate, to be associated with autism spectrum disorder (ASD). Results for specific complications, such as maternal diabetes and hypertension, have not been uniformly consistent and should be investigated independently in relation to ASD in a large community-based sample. The Study to Explore Early Development (SEED), a US multisite case-control study, enrolled children born in 2003-2006 at 2-5 years of age. Children were classified into three groups based on confirmation of ASD (n = 698), non-ASD developmental delay (DD ; n = 887), or controls drawn from the general population (POP ; n = 979). Diagnoses of any diabetes or hypertensive disorder during pregnancy were identified from prenatal medical records and maternal self-report. Logistic regression models estimated adjusted odds ratios (aOR) and confidence intervals (CI) adjusting for maternal age, race/ethnicity, education, smoking during pregnancy, and study site. Models for hypertension were additionally adjusted for parity and plurality. Among 2,564 mothers, we identified 246 (9.6%) with any diabetes and 386 (15.1%) with any hypertension in pregnancy. After adjustment for covariates, any diabetes during pregnancy was not associated with ASD (aOR = 1.10 [95% CI 0.77, 1.56]), but any hypertension was associated with ASD (aOR = 1.69 [95% CI 1.26, 2.26]). Results were similar for DD, and any diabetes (aOR = 1.29 [95% CI 0.94, 1.78]) or any hypertension (aOR = 1.71 [95% CI 1.30, 2.25]). Some pregnancy complications, such as hypertension, may play a role in autism etiology and can possibly serve as a prompt for more vigilant ASD screening efforts. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : We studied if common complications in pregnancy are associated with autism spectrum disorder (ASD) in a large sample of mothers and children. Our results show an association between conditions marked by high blood pressure and ASD, but no association with conditions marked by high blood sugar and ASD. Associations were similar for children who had a developmental disorder that was not ASD, suggesting that this relationship may not be specific to ASD.

Sleep disturbances are frequent and varied in autism spectrum disorder (ASD). Growing evidence suggests that sleep problems in children with ASD are driven by their clinical characteristics and psychiatric comorbidities. Therefore, the wide range of reported sleep disturbances reflects the marked heterogeneity of clinical pictures in ASD. Whether sleep disturbances and their various forms may, in turn, account for at least part of the phenotypical variability of ASD is a crucial question discussed in this review. We first outline studies both validating and challenging a bidirectional theoretical framework for sleep disorders in children with ASD. We then propose to extend this model by including cognition and sensory processing as key factors in the vicious circle linking sleep disorders and autistic symptoms. WHAT THIS PAPER ADDS : There is a bidirectional interplay between autism symptoms and sleep disturbances. Sleep influence on daytime cognitive and sensory skills should be further investigated.

Many individuals with autism report generally low quality of life (QoL). Identifying predictors for pathways underlying this outcome is an urgent priority. We aim to examine multivariate patterns that predict later subjective and objective QoL in autistic individuals. Autistic characteristics, comorbid complaints, aspects of daily functioning, and demographics were assessed online in a 2-year longitudinal study with 598 autistic adults. Regression trees were fitted to baseline data to identify factors that could predict QoL at follow-up. We found that sleep problems are an important predictor of later subjective QoL, while the subjective experience of a person’s societal contribution is important when it comes to predicting the level of daily activities. Sleep problems are the most important predictor of QoL in autistic adults and may offer an important treatment target for improving QoL. Our results additionally suggest that social satisfaction can buffer this association. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : Many individuals with autism report generally low quality of life (QoL). In this study, we looked at factors that predict long-term QoL and found that sleep problems are highly influential. Our results additionally suggest that social satisfaction can buffer this influence. These findings suggest that sleep and social satisfaction could be monitored to increase QoL in autistic adults.

Age-related changes in resting-state (RS) neural rhythms in typically developing children (TDC) but not children with autism spectrum disorder (ASD) suggest that RS measures may be of clinical use in ASD only for certain ages. The study examined this issue via assessing RS peak alpha frequency (PAF), a measure previous studies, have indicated as abnormal in ASD. RS magnetoencephalographic (MEG) data were obtained from 141 TDC (6.13-17.70 years) and 204 ASD (6.07-17.93 years). A source model with 15 regional sources projected the raw MEG surface data into brain source space. PAF was identified in each participant from the source showing the largest amplitude alpha activity (7-13 Hz). Given sex differences in PAF in TDC (females > males) and relatively few females in both groups, group comparisons were conducted examining only male TDC (N = 121) and ASD (N = 183). Regressions showed significant group slope differences, with an age-related increase in PAF in TDC (R(2) = 0.32) but not ASD (R(2) = 0.01). Analyses examining male children below or above 10-years-old (median split) indicated group effects only in the younger TDC (8.90 Hz) and ASD (9.84 Hz ; Cohen’s d = 1.05). In the older ASD, a higher nonverbal IQ was associated with a higher PAF. In the younger TDC, a faster speed of processing was associated with a higher PAF. PAF as a marker for ASD depends on age, with a RS alpha marker of more interest in younger versus older children with ASD. Associations between PAF and cognitive ability were also found to be age and group specific.

9. Goetz GL, Rodriguez G, Hartley SL. Actor-partner examination of daily parenting stress and couple interactions in the context of child autism. Journal of family psychology : JFP : journal of the Division of Family Psychology of the American Psychological Association (Division 43). 2019.

Parents of children with autism spectrum disorder (ASD) are at risk for poor couple relationship quality. The goal of the current study was to understand actor and partner associations between daily level of parenting stress and perceived couple interactions using a 14-day daily diary in 186 families of children with ASD. A comparison group of 182 families of children without a neurodevelopmental disability was included to determine if actor and partner associations differed in a context of child ASD. On each day of the 14-day diary, parents independently rated their daily level of parenting stress (7-point scale) and reported on the perceived presence of different types of positive (e.g., hugged and kissed) and negative (e.g., critical comment) couple interactions. Multilevel models were used to examine actor and partner effects, and their interaction, in mothers and fathers and by group (ASD vs. comparison). Results indicated that actor daily level of parenting stress negatively covaried with perceived positive couple interactions in mothers in both groups. In contrast, actor daily level of parenting stress positively covaried with perceived positive couple interactions in fathers in the ASD group. There was a significant interaction between actor and partner daily level of parenting stress for perceived negative couple interactions in both mothers and fathers. Specifically, one’s own daily level of parenting stress was more strongly positively related to her/his perceived negative couple interactions on days when her/his partner also had high parenting stress. This interaction was stronger in mothers in the ASD versus comparison group. Implications for family interventions are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The Autism impact measure (AIM) is a caregiver-reported questionnaire assessing autism symptom frequency and impact in children, previously shown to have good test-retest reliability, convergent validity and structural validity. This study extended previous work by exploring the AIM’s ability to discriminate between ’known-groups’ of children, and estimating thresholds for clinically important responses. Data were collected online and electronically on computer and mobile devices ; hence, it was also possible to confirm other psychometric properties of the AIM in this format. This study provides confirmatory and additional psychometric validation of the AIM. The AIM offers a valid, quick and inexpensive method for caregivers to report core symptoms of autism spectrum disorder (ASD) including communication deficits, difficulties with social interactions and repetitive behaviors.

Many studies have reported abnormal gut microbiota in individuals with Autism Spectrum Disorders (ASD), suggesting a link between gut microbiome and autism-like behaviors. Modifying the gut microbiome is a potential route to improve gastrointestinal (GI) and behavioral symptoms in children with ASD, and fecal microbiota transplant could transform the dysbiotic gut microbiome toward a healthy one by delivering a large number of commensal microbes from a healthy donor. We previously performed an open-label trial of Microbiota Transfer Therapy (MTT) that combined antibiotics, a bowel cleanse, a stomach-acid suppressant, and fecal microbiota transplant, and observed significant improvements in GI symptoms, autism-related symptoms, and gut microbiota. Here, we report on a follow-up with the same 18 participants two years after treatment was completed. Notably, most improvements in GI symptoms were maintained, and autism-related symptoms improved even more after the end of treatment. Important changes in gut microbiota at the end of treatment remained at follow-up, including significant increases in bacterial diversity and relative abundances of Bifidobacteria and Prevotella. Our observations demonstrate the long-term safety and efficacy of MTT as a potential therapy to treat children with ASD who have GI problems, and warrant a double-blind, placebo-controlled trial in the future.

Some evidence suggests that bilingualism improves communication and cognitive skills which are often impaired in autism. However, diagnosing autism in bilinguals may suffer a cultural bias, which can affect the investigation of bilingualism and autism. Therefore, the current study investigates relations between autistic-like traits (ALTs) and bilingualism in a general population sample of 394 children (M age = 8 ;3). Within the high-scoring group on the ALT measure, monolinguals had significantly higher ALT scores than bilinguals. There were no differences between monolinguals and bilinguals in the low-scoring group. Across the whole sample, age and structural language skills accounted for 35% variance in ALTs, while bilingualism had no effect on ALTs. Furthermore, structural language skills explained more variance in ALTs among bilinguals than among monolinguals.

Abstracts : Objective : In current international research, early intervention in children with autism-spectrum disorder (ASD) focuses on naturalistic developmental behavioral interventions (NDBI). The manualized Frankfurt Early Intervention Program for preschool-aged children with ASD (A-FFIP) implements NDBI principles within a low-intensity approach of 2 h intervention/week. The present case-control study established effect sizes of change in autistic symptoms, comorbid behavioral problems as well as IQ after one year. Methodology : An intervention group (N = 20 ; age : 3.4-7.9 years) and a treatment-as-usual control group (N = 20 ; age : 3.2-7.3 years) of children with ASD were matched for developmental and chronological age. The outcome measures used were the ADOS severity score, the Child Behavior Checklist, and cognitive development. Results : After one year, the A-FFIP group showed a trend towards greater improvement in autistic symptoms (eta2 = .087 [95 %-CI : .000-.159]) and significantly greater improvements in cognitive development (eta2 = .206 [CI : .012-.252]) and global psychopathology (eta2 = .144 [CI : .001-.205]) compared to the control group. Conclusion : The efficacy of A-FFIP should be established in a larger, sufficiently powered, randomized controlled study.

Children with autism spectrum disorder (ASD) have trouble with non-verbal communication, which is strongly associated with poor social function.(1) There are few evidence-based interventions for children with ASD, so tutors find it difficult to teach non-verbal communication skills. This article is protected by copyright. All rights reserved.

Determining a patient’s dental age is essential from the dental standpoint but can also have connotations of a forensic, anthropological and medicolegal nature. In this study, we assessed the correspondence between dental age and chronological age in a group of 50 children with autism spectrum disorders, with a chronological age range of 3-17 years. The dental age was calculated using panoramic radiography images, applying linear regression models derived from the classical indices by Nolla and Demirjian. In 2 of every 3 boys, the dental age was ahead of the chronological age, and in almost 1 of every 3 cases, the difference was >/= 12 months. In the girls, conversely, we found no significant differences between dental age and chronological age.

This four-week, randomized, double-blind, placebo-controlled study investigated the effects of Lactobacillus plantarum PS128 (PS128) on boys with autism spectrum disorder (ASD) aged 7-15 in Taiwan. All subjects fulfilled the criteria for ASD diagnosis of DSM-V and the Autism Diagnostic Interview-Revised (ADI-R). Questionnaires used for the primary outcome measure include the Autism Behavior Checklist-Taiwan version (ABC-T), the Social Responsiveness Scale (SRS) and the Child Behavior Checklist (CBCL). The Swanson, Nolan, and Pelham-IV-Taiwan version (SNAP-IV) and the Clinical Global Impression-improvement (CGI-I) were used for the secondary outcome measure. The results showed that PS128 ameliorated opposition/defiance behaviors, and that the total score of SNAP-IV for younger children (aged 712) improved significantly compared with the placebo group. Additionally, several elements were also notably improved in the PS128 group after 28-day consumption of PS128. Further studies are needed to better clarify the effects of PS128 for younger children with ASD on broader symptoms.

Individuals with autism spectrum disorder (ASD) exhibit impaired adult facial processing, as shown by the N170 event-related potential. However, few studies explore such processing in mothers of children with ASD, and none has assessed the early processing of infant faces in these women. Moreover, whether processing of infant facial expressions in mothers of children with ASD is related to their response to their child’s needs (maternal sensitivity [MS]) remains unknown. This study explored the N170 related to infant faces in a group of mothers of children with ASD (MA) and a reference group of mothers of children without ASD. For both emotional (crying, smiling) and neutral expressions, the MA group exhibited larger amplitudes of N170 in the right hemisphere, while the reference group showed similar interhemispheric amplitudes. This lateralization effect within the MA group was not present for nonfaces and was stronger in the mothers with higher MS. We propose that mothers of ASD children use specialized perceptual resources to process infant faces, and this specialization is mediated by MS. Our findings suggest that having an ASD child modulates mothers’ early neurophysiological responsiveness to infant cues. Whether this modulation represents a biological marker or a response given by experience remains to be explored. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : When mothers of children with autism spectrum disorder (ASD) see baby faces expressing emotions, they show a right-sided electrical response in the brain. This lateralization was stronger in mothers who were more sensitive to their children’s needs. We conclude that having a child with ASD and being more attuned to their behavior generates a specialized pattern of brain activity when processing infant faces. Whether this pattern is biological or given by experience remains to be explored.

AIM : To assess the accuracy of the Childhood Autism Rating Scale (CARS) through systematic review and meta-analysis. METHOD : Studies that provided quantitative values for the reliability and validity for all versions of CARS were searched through MEDLINE, CINAHL, PsycINFO, Embase, and OpenDissertations. RESULTS : A total of 24 studies with 4433 participants were included in our analysis. Meta-analysis showed that the summary Cronbach’s alpha regarding a team of physicians and psychologists or others subgroup, derived from six studies (952 participants), was considered to be acceptable at 0.90 (95% confidence interval, 0.87-0.92) with moderate heterogeneity. Analysis of two ’low risk of bias’ studies on the criterion validity for CARS with a cut-off of 30 and DSM-IV resulted in sensitivity of 0.86 and 0.71 and specificity of 0.79 and 0.75. INTERPRETATION : Through the results of the current systematic review and meta-analysis, the internal consistency can be considered to be acceptable for a team of physicians and psychologists or others subgroup. In terms of the criterion validity, the sensitivity was thought to be acceptable although the specificity was not, suggesting that CARS should be used along with other confirmatory tools. WHAT THIS PAPER ADDS : The Childhood Autism Rating Scale can be considered as a supplementary diagnostic tool for autism spectrum disorder.

Autism is associated with a range of costs. This paper reviews the literature on estimating the economic costs of autism spectrum disorder (ASD). More or less 50 papers covering multiple countries (US, UK, Australia, Canada, Sweden, the Netherlands, etc.) were analysed. Six types of costs are discussed in depth : (i) medical and healthcare service costs, (ii) therapeutic costs, (iii) (special) education costs, (iv) costs of production loss for adults with ASD, (v) costs of informal care and lost productivity for family/caregivers, and (vi) costs of accommodation, respite care, and out-of-pocket expenses. A general finding is that individuals with ASD and families with children with ASD have higher costs. Education costs appear to be a major cost component for parents with children with ASD.

The purpose of the current study was to identify profiles of self-regulation across executive functioning (EF) and emotion regulation (ER) and examine profiles’s impact on treatment outcomes. Participants included 100 preschoolers (Mage = 4.73, 75% Male, 79% Hispanic) including 37 with autism spectrum disorder and attention-deficit/hyperactivity disorder (ASD+ADHD), 32 with ADHD-only, and 31 typically developing children. Parents and teachers reported on children’s EF, ER, ASD, and ADHD symptoms. Children were administered an EF battery and observed for ER during a frustration task. Children participated in an intensive behavioral summer treatment program (STP-PreK) aimed at improving school readiness across behavioral, academic, and self-regulation domains. Latent profile analyses produced 4 profiles : (a) Low ER and EF Deficits, (b) High ER Deficits, (c) High EF Deficits, and (d) Moderate ER and EF Deficits. ASD and ADHD symptoms predicted lower membership probability within the Low ER and EF Deficits Profile and higher membership probability within the Moderate ER and EF Deficits Profile. However, only ASD symptoms predicted membership within the High EF Deficits Profile. Only ADHD symptoms predicted membership within the High ER Deficits Profile. Even after accounting for diagnostic symptoms, profile membership was predictive of treatment response across behavioral and academic domains. Children in the High EF Deficits Profile experienced the largest gains. Results highlight the specificity of self-regulation deficits within and across diagnoses. Self-regulation profiles demonstrated clinical utility in predicting treatment response above traditional symptom based classifications, providing evidence for the use of transdiagnostic approaches.

To advance what is known about how emotions affect memory in autism spectrum disorder (ASD), we examined emotional false memory for negative, positive, and neutrally valenced photographs comprising scripts of everyday events in a verbal IQ-case matched sample of youth ages 8-14 with ASD (N = 38) and typical development (TYP, N = 38). The groups exhibited many similarities. Their task performance during a recognition task including previously seen and unseen photographs was largely comparable. They evidenced high hit rates for previously viewed photographs, and low false alarm rates for lure photographs that were inconsistent with the scripts. Both ASD and TYP groups showed relatively higher false alarms for lure photographs depicting previously unseen causes of scenario outcomes (causal errors) compared to errors for script-consistent lure photographs that showed extra potentially related events (gap-filling errors). In both groups, task performance was associated with verbal working memory, but not attention deficit hyperactivity, anxiety, or depression symptoms. However, the ASD group made more causal and gap-filling errors on negative and positive, but not neutral, lures compared to TYP, indicating that viewing emotionally valenced stimuli made it harder to discriminate previously seen and unseen photographs. For the ASD group, task performance was associated with compulsive, ritualistic, and sameness behaviors and stereotypic and restricted interests. Findings suggest that the integration of cognition and emotion in ASD is altered and associated with the presence of repetitive behaviors. The impact of these results on the lives of individuals with ASD and implications for psychosocial interventions are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

There is a pressing need to better characterize the college-bound population of individuals with autism spectrum disorder (ASD), as prior studies have included small samples, consisting of individuals who are either recruited due to diagnosis or are treatment seeking. As postsecondary institutions look to respond to the growing need for support services for individuals with ASD, insights derived from large, population-based samples is a necessity. The current study included a sample of over 2000 incoming postsecondary students who self-identified with ASD as a part of surveys distributed by institutions nationally. The impact of heterogeneity (gender, comorbid attention-deficit/hyperactivity disorder [ADHD], and/or learning disability) on demographic characteristics, and psychosocial (psychological health, interpersonal self-confidence) and academic (self-regulated learning, intellectual self-confidence) domains critical for success in postsecondary education were compared to a matched sample of students with ADHD or no diagnoses. College-bound students with ASD broadly endorsed similar rates of ADHD, LD, and psychological disorder comorbidity to clinic-referred samples, and were more similar than different from their typically developing peers. A comorbid diagnosis of ADHD was associated with greater academic disengagement. Females with ASD and those with any comorbid disorder were more likely to self-report poorer psychological health. Findings revealed that self-reported levels of functioning in critical domains differed by self-reported comorbid disorders and gender. Findings have implications for targeted support service recommendations based on unique sources of heterogeneity (e.g., gender, presenting comorbid disorders) and are detailed in the current study. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : College-bound students with ASD feel academically competent ; however feel less confident with their peers. Students with ASD and another diagnosis (e.g., ADHD, learning disability) and girls with ASD may be particularly at risk of experiencing poorer psychological health while enrolled in postsecondary education. Using this information, postsecondary institutions can provide more targeted support services to students with ASD enrolled in postsecondary education.

Autism is a known as severe neurobehavioral syndrome, with males affected more often than females. Previous studies have revealed that microRNAs (miRNAs) play a critical role in the search for novel therapeutic strategies for autism. Therefore, we evaluate the ability of miR-153 to influence brain-derived neurotrophic factor (BDNF) of autism as well as proliferation and apoptosis of hippocampal neuron through the JAK-STAT signaling pathway by targeting leptin receptor (LEPR). Firstly, the autistic mice models were established and Morris water maze was employed for the analysis of the learning ability and memory of the mice. Besides, in vitro experiments were conducted with the transfection of different mimic, inhibitor or siRNA into the hippocampal neuron cells, after which the effect of miR-153 on LERP and the JAK-STAT signaling pathway-related factors was investigated. Next, MTT assay and flow cytometry assay were conducted to evaluate cell proliferation, cell cycle and apoptosis respectively following transfection. The results revealed that there was a significant decrease in learning ability and memory in the autistic mice along with a reduction in the positive expression rate of BDNF and serious inflammatory reaction. LEPR was confirmed as a target gene of miR-153 by the dual luciferase reporter gene assay. After transfection of overexpressed miR-153, LEPR and the JAK-STAT signaling pathway were inhibited followed by an increase in BDNF and enhancement of cell proliferation. In conclusion, the high expression of miR-153 can inhibit activation of JAK-STAT signaling pathway by LEPR, thus improving BDNF expression and the proliferative ability of hippocampal neurons.

Mounting evidence supports that LINE-1 (L1) retrotransposition can occur postzygotically in healthy and diseased human tissues, contributing to genomic mosaicism in the brain and other somatic tissues of an individual. However, the genomic distribution of somatic human-specific LINE-1 (L1Hs) insertions and their potential impact on carrier cells remain unclear. Here, using a PCR-based targeted bulk sequencing approach, we profiled 9,181 somatic insertions from 20 postmortem tissues from five Rett patients and their matched healthy controls. We identified and validated somatic L1Hs insertions in both cortical neurons and non-brain tissues. In Rett patients, somatic insertions were significantly depleted in exons-mainly contributed by long genes-than healthy controls, implying that cells carrying MECP2 mutations might be defenseless against a second exonic L1Hs insertion. We observed a significant increase of somatic L1Hs insertions in the brain compared with non-brain tissues from the same individual. Compared to germline insertions, somatic insertions were less sense-depleted to transcripts, indicating that they underwent weaker selective pressure on the orientation of insertion. Our observations demonstrate that somatic L1Hs insertions contribute to genomic diversity and MeCP2 dysfunction alters their genomic patterns in Rett patients.